Iwahashi H, Itoh N, Yamagata K, Imagawa A, Nakajima H, Tomita K, Moriwaki M, Waguri M, Yamamoto K, Miyagawa J, Namba M, Hanafusa T, Matsuzawa Y
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Cytokines Cell Mol Ther. 1998 Mar;4(1):45-51.
Mononuclear cell infiltration into the islets of the pancreas (insulitis) is characteristic of autoimmune diabetes. T lymphocytes are the predominant subpopulation seen in insulitis, and are involved in the autoimmune process. Insulin-producing beta cells are thought to be destroyed by cytotoxic T cells, cytokines or nitric oxide, and beta-cell death occurs, at least partly, via apoptosis. Beta-cell death induced by cytokines is inhibited by Bcl-2, suggesting its potential as a tool for gene therapy. The Fas/Fas-ligand system plays a critical role in inducing insulitis and overt diabetes in nonobese diabetic (NOD) mice, a model of autoimmune diabetes. T-cell receptor gene usage in infiltrating T cells is not restricted in NOD mice, but there are some observations indicating relative restriction in human IDDM patients. Preventive strategies might be developed by focusing on these molecules involved in beta-cell destruction. The establishment of screening techniques for detecting prediabetic patients is also necessary to allow successful intervention.
单核细胞浸润胰腺胰岛（胰岛炎）是自身免疫性糖尿病的特征。T淋巴细胞是胰岛炎中主要的亚群，并参与自身免疫过程。产生胰岛素的β细胞被认为会被细胞毒性T细胞、细胞因子或一氧化氮破坏，并且β细胞死亡至少部分是通过凋亡发生的。细胞因子诱导的β细胞死亡受到Bcl-2的抑制，这表明其作为基因治疗工具的潜力。Fas/Fas配体系统在非肥胖糖尿病（NOD）小鼠（一种自身免疫性糖尿病模型）中诱导胰岛炎和显性糖尿病方面起关键作用。浸润性T细胞中T细胞受体基因的使用在NOD小鼠中不受限制，但有一些观察结果表明在人类胰岛素依赖型糖尿病（IDDM）患者中存在相对限制。通过关注这些参与β细胞破坏的分子，可能会制定预防策略。建立用于检测糖尿病前期患者的筛查技术对于成功干预也很有必要。
